CD47 is expressed on the surface of all human solid tumors. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRP alpha, a cell surface receptor expressed on macrophages. Binding of CD47 to SIRP alpha suppresses macrophage phagocytosis of tumor cells. Thus, CD47 has been dubbed a “don't eat me” signal. See, e.g., Willingham et al., (2012) Proc. Natl. Acad. Sci. USA (Published online before print Mar. 26, 2012, doi: 10.1073/pnas.1121623109.)
Anti-CD47 antibody therapy has been proposed as a new therapeutic approach for treating solid tumors. Anti-CD47 antibodies bind CD47 and hinder or prevent the binding of CD47 to SIRP alpha on macrophages. Thus, the “don't eat me” signal would be squelched. Preliminary work has suggested this therapeutic path has promise. However, concerns about specificity and adverse side effects have arisen.
There is a need in the art for improved therapeutic agents for treating solid tumors.